Probing DNA polymerase function with synthetic nucleotides

Transmission of the genetic information from the parental DNA strand to the offspring is crucial for the survival of any living species. In nature this process is catalyzed by the replication machinery in which DNA polymerases are essential for the entire DNA synthesis. Recently, a wealth of valuable new insights into DNA polymerase mechanisms were gained through application of carefully designed synthetic nucleotides and oligonucleotides in functional enzyme studies. The applied analogues exhibit features that differ in certain aspects from their natural counterparts and thus, allow investigation of the involvement and efficacy of a chosen particular aspect on the entire complex enzyme mechanism. This review will focus on a depiction of the synthetic efforts that were undertaken towards the targeted synthesis of nucleotide analogues with carefully altered properties. The synthetic endeavors will be discussed in the context of the motivation and the problem under investigation.